Dissertation
PIGMENT GENETICS AS TOLD BY CRASHER: CHARACTERIZATION OF A NOVEL ZEBRAFISH ALBINISM MODEL THROUGH GENETIC ENGINEERING AND GENE EXPRESSION ANALYSIS
Washington State University
Doctor of Philosophy (PhD), Washington State University
01/2021
DOI:
https://doi.org/10.7273/000003343
Handle:
https://hdl.handle.net/2376/123002
Abstract
Melanin is a black pigment that protects DNA from ultraviolet (UV) damage by absorbing excess energy. In addition, melanin allows organisms to blend into their backgrounds to provide camouflage from predators. Melanin is produced in a process called melanogenesis. When melanogenesis is altered, diseases such as albinism result. Albinism can result in increased skin cancer risk. Conversely, black pigment cell (melanocyte) development pathways can be misregulated, causing excessive melanocyte growth that leads to melanoma (cancer of melanocytes). Zebrafish are an emerging model organism to study pigment disorders due to their high fecundity, visible melanin development in melanophores (melanocytes in mammals) from 24 hours post fertilization; and conserved melanogenesis pathways. Here, I review the development of melanocytes/melanophores, the process of melanogenesis, the genes that are critical for both melanocyte/melanophore development and melanogenesis, and how these processes are altered in disease. We define a new zebrafish model for albinism which we have named crasher. We show crasher is caused by mutations in ap3d1, that melanogenesis enzyme gene expression is altered, and that ap3d1 is important for melanophore survival. I also use RNA-seq data to address why the homozygous lethal crasher mutation impacts the health of the fish. I find crasher mutants have increased expression in immune pathways and decreased expression in energy pathways that may contribute to poor health outcomes. Finally, we discuss how crasher and other pigment cell development mutants may be used to study albinism and melanoma.
Metrics
51 File views/ downloads
36 Record Views
Details
- Title
- PIGMENT GENETICS AS TOLD BY CRASHER: CHARACTERIZATION OF A NOVEL ZEBRAFISH ALBINISM MODEL THROUGH GENETIC ENGINEERING AND GENE EXPRESSION ANALYSIS
- Creators
- Samantha Neuffer
- Contributors
- Cynthia D Cooper (Advisor)Allison Coffin (Committee Member)Steven Sylvester (Committee Member)Jennifer Watts (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Molecular Biosciences, School of
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Publisher
- Washington State University
- Number of pages
- 217
- Identifiers
- 99900652103501842
- Language
- English
- Resource Type
- Dissertation